来自威斯康星大学麦迪逊分校的研究人员发现了一些很罕见的HIV病毒阳性患者,如何在没有抗逆转录病毒药物介入的情况下,就能对抗艾滋病病毒的机制,这一发现将有助于科学家们进一步研发针对艾滋病毒/艾滋病的疫苗。

-2012年11月1日《自然》

中文翻译


【题目】疫苗诱导CD8+ T细胞控制AIDS病毒复制

【译文】人类免疫缺陷病毒(HIV)疫苗的开发可能受助于对一些稀有病例即HIV感染个体控制病毒复制的完整理解。大多数这些控制因子表达组织相容性等位基因HLA-B*57或HLA-B*27。这些等位基因还是与低血浆病毒浓度最有力的关联,但这些个体中的控制机制还不完全清楚。本研究我们接种了表达Mamu-B*08的印度恒河猴,这是一种HLA-B*27介导的精英控制的动物模型,具有三个Mamu-B*08限制的CD8+ T细胞抗原表位,并证实了这些接种的动物控制着高度致病性猴免疫缺陷病毒(SIV) mac239的复制。对抗血液、淋巴结及结肠中这些Vif和Nef表位的高频率CD8+ T细胞与病毒控制密切相关。此外,抵抗Nef RL10表位(Nef氨基酸137-146)的CD8+ T细胞反应频率与减少的急性期病毒血症显著相关。最后,在慢性期8个接种者中的2个丢失了病毒复制的控制,伴随三种靶向表位的逃脱,与病毒复制控制中这三种CD8+ T细胞反应相关。我们的发现表明精细地靶向疫苗诱导的特异性CD8+ T反应可以控制AIDS病毒的复制。

英文原稿


[Title]: Vaccine-induced CD8+ T cells control AIDS virus replication

[Authors]:Philip A. Mudd,1, 2 Mauricio A. Martins,3 Adam J. Ericsen,1 Damien C. Tully,4 Karen A. Power,4 Alex T. Bean,1 Shari M. Piaskowski,1 Lijie Duan,5 Aaron Seese,4 Adrianne D. Gladden,4 Kim L. Weisgrau,1 Jessica R. Furlott,1 Young-il Kim,6 Marlon G. Veloso de Santana,7 Eva Rakasz,8 Saverio Capuano III,8 Nancy A. Wilson,1, 8 Myrna C. Bonaldo,7 Ricardo Galler,9 Ashley T. Haase,5 Jeffrey D. Lifson,11 Todd M. Allen4 & David I. Watkins3

[Abstract]:Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus. Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27. These alleles remain by far the most robust associations with low concentrations of plasma virus, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control, with three Mamu-B*08-restricted CD8+ T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8+ T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8+ T-cell response against the Nef RL10 epitope (Nef amino acids 137-146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8+ T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8+ T-cell responses can control replication of the AIDS virus.

原文地址

http://www.nature.com/nature/journal/v491/n7422/full/nature11443.html

 

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